The long-term objective of this subproject is to increase understanding of the function of endogenous neuropeptides and their receptors in the control of voluntary alcohol preference in an animal model of ethanol consumption. The proposed research will characterize the effects of administrations of the neuropeptides cholecystokinin and bombesin, their specific receptor blockers, and serotonin receptor blockers, on the free- choice of alcohol solutions in outbred and inbred rats. The specific aim of the experimental designs is to examine the biological receptor processes and a neurotransmitter system involved in neuropeptide regulation of preference for, and intake of alcohol in rats. Outbred Wistar rats and rats selectively bred for high, control, and low initial alcohol sensitivity will be motivated to consume alcohol solution by water or food deprivation, or periodic access to alcohol under ad lib conditions, with a successive or simultaneous choice of water. Peptides, peptide receptor blockers, and serotonin receptor blockers will be injected peripherally across a range of doses and delay times, singly and in combinations, and alcohol preference will be measured. Interactions of these chemical agents will be determined by isobolographic analysis as infra-, supra-, or dose-additive. Results will allow a conclusion whether the known inhibitory effects of cholecystokinin and bombesin on alcohol preference are mediated through a specific type of endogenous neural peptide receptor, and whether these effects depend upon the activity of the serotonin neurotransmitter system. Evidence will be also provided to determine if endogenous cholecystokinin- and bombesin-like peptides act physiologically to regulate alcohol preference. Research results will provide an explanation of the neuropeptide processes involved in control of alcohol consumption. Obtained preclinical data will provide a basis for pharmacological, nutritional, and psychophysiological interventions to correct human disorders of alcohol abuse and alcoholism.